Potassium Channels Flashcards
What is the structure of a VG K+ channel alpha subunit?
Intracellular N terminus TM1 TM2 TM3 TM4 TM5 Pore loop TM6 Intracellular C terminus
How many subunits come together for form a channel?
4
N terminal interacts with other alpha subunits
Typical of the same family e.g. Kv1.1 and kv1.1/kv1.2 etc
Why is TM4 of the alpha subunit important.
Contains a positive charged residue every 3rd amino acid (arginine or lysine)
Contributes to voltage sensitivity
What is a K+ channel antagonist?
Tetraethylammonium (TEA)
What TMDs are conserved across k+ channels?
5 and 6
What does the p loop contain?
The 30 amino acid selectivity pore
Why are k+ channels important?
Set RMP
Repolarisation
Conductance and cell time constants
The are 2 types of K+ channels…what are they?
Leak channels
Gated channels
What channels are in the category of leak channels?
Inward rectifiers (kir) which favour ion influx Tandem pore outward rectifiers (K2P)
What types of k+ channels fall under the category of gated channels?
Volatage gated - conductance regulates AP Length Ligand gated (e.g. By gpcrs, calcium, cyclic nucelotides)
What are some of the conduction properties of VG K+ channels?
Intracellular and extracellular entry ways lined with negative aminoacids
Pore length is 45A
Pore diameter varies throughout channel
What aminoacids are essential for k+ selectivity on selectivity pore?
Conserved GYG motif
What are the 4 mechanisms which allow k+ selectivity?
Helix dipole
Muiltple occupancy
Customised oxygen cages
Plenty of water
What is a helix dipole?
Positive to negative charged helix in pore to overcome electrostatic destabilisation
Lowers electrostatic barrier of membrane
Points towards centre of cavity
What does multiple occupancy allows for?
2 K+ in selectivity pore
1 K+ in cavity
Pushes ions through channel
What is the purpose of oxygen cages?
Co ordinate dehydrated K+ ions (must be dehydrated to pass through as internal helix creates hydrophobic environment)
What cannot sodium ions fit through?
Sodium ions too small for perfect oxygen cage organisation
What is the advantage of water for K+ selectivity?
Water in larger cavity stabilises ion and helps ion overcome electrostatic destabilisation due to low dielectric bilayer
In the centre of the bilayer polarising ability of ion lowest = high energy. Water helps minimise this
What are the two types of channel inactivation?
N type (N terminal ball plugs channel) C type (narrowing of the pore..contraction of outer mouth)
What channels use N terminal inactivation?
Kv1.3 and kv1.4
Where might the inactivation peptide be located?
May be in the alpha Or beta subunit of the potassium channel
What do accessory subunits do?
Change the properties of the channel
E.g. Channel regulation, quicker inactivation (n terminal thether plug)
Kv1 (not kv1.4) is associated with beta1.1 subunit which increase inactivation through n terminal plug
What is required for a single channel to open?
4 subunits need to be in the right state/confirmation to open properly
Open probability varies between individual channels but averaged together many channels from a united current as individual firing properties become negligible
What kv channel is HVA?
Kv3 (opens at high levels of depolarisation)
What kv channel is LVA?
Kv1+4
What is the role of HVA channels?
Repolarisation of AP
What is the purpose of LVA Kv channels?
Maintain RMP and regulate threshold for AP firing
What is tetraethylammonium more selective for at low doses?
Kv3
What is dendrotoxin selective for?
Kv1
What channels set the RMP?
Leak channels - esp Tandem pore outward rectifiers e.g. k2P
What happens if we increase the number of kv1 channels?
Will increase the threshold for AP firing as more will open at smaller depolarisations (more k+ efflux therefore more sodium needed to reach threshold)
What would happen to an AP if we increased the number fo kv3 channels?
AP will be shorter as repolarisation will occur faster
